P784: CYCLOSPORINE WITH THROMBOPOIETIN RECEPTOR AGONIST IN THE TREATMENT OF APLASTIC ANEMIA WITH OR WITHOUT ANTI-THYMOCYTE IMMUNOGLOBULIN：A MULTICENTER REAL WORLD RETROSPECTIVE STUDY
Authors: Miao Chen, Bing Han
Journal: HemaSphere (2023)

Topic: 12. Bone marrow failure syndromes incl. PNH - Clinical Background: Acquired idiopathic aplastic anemia (AA) is mostly an immune mediated bone marrow failure disease. Immunosuppressive therapy (IST) is the front-line treatment for AA patients who are not candidates for stem cell transplantation. Standard IST with anti-thymocyte globulin (ATG) plus cyclosporine (CSA) produces a hematologic response rate of 60 to 80% for severe AA (SAA) patients. Eltrombopag (EPAG) showed efficacy for relapsed refractory AA, and the response rate of ATG combining CSA and EPAG as first-line treatment for SAA patients was as high as 94%. The addition of EPAG to standard IST improved the rate, rapidity, and strength of hematologic response. At present, ATG is still the forefront recommendation for SAA and transfusion dependent non-severe aplastic anemia (TD-NSAA). However, in China, ATG is often not used due to lack of experience in many centers, hospital admission difficulties, high costs, long hospital stay and relatively severe side effects. A prospective cohort registry study involving 22 AA centers in China showed that only 22.2% of the newly diagnosed AA patients (SAA or TD-AA) received standard IST (including ATG) as guideline-recommended. EPAG showed good efficacy and safety for AA, CSA combining EPAG may be an appropriate alternative option. We retrospectively collected the data from multi-centers of patients with newly diagnosed AA who had been treated with CsA+ATG+EPAG or CsA+EPAG, and intend to compare the efficacy, side-effects, and the outcome of the two regimens in the real world. Aims: To compare cyclosporine (CSA) combining eltrombopag (EPAG) with or without anti-thymocyte globulin (ATG) in patients with untreated aplastic anemia (AA) in the real world. Methods: Patients with previously untreated adult AA patients who received CSA and EPAG combined with or without ATG as front-line treatment in 13 medical centers in northern China were enrolled and divided into ATG combining CSA and EPAG group (group A) and CSA plus EPAG group (group B). The efficacy and safety were compared in all patients and in different disease severity subgroups. Factors that could possibly affect the response rate were analyzed. Results: 89 patients were enrolled. 51 patients were treated with CSA+ATG+ EPAG (group A) and 38 patients were treated with CSA + EPAG (group B). The median initial and maximum dose of EPAG was 50mg Q.D. and 75 mg Q.D., respectively. The 6-month overall response rate (ORR)/complete response rate (CRR) was 73.3%/24.4% and 60.6%/27.3% in group A and B, respectively (P>0.1). For severe aplastic anemia (SAA) patients, the 6-month OR was 74.1% vs. 50% and 6-month CR was 25.9% vs 20% in group A and B (P>0.1). Multivariate analysis showed gender significantly affects the 6-month OR (P=0.017, OR 6.045, 95% CI: 1.377-26.546) and time from disease onset to treatment significantly affected the 12-month CR (P=0.026, OR 0.263,95% CI: 0.081-0.852). The 6-month ORR for NSAA and SAA treated with CSA plus EPAG was 75.0% vs. 52.4% and the CR was 41.7% vs. 19.0%(P>0.1). Multivariate analysis showed only gender significantly impact 6-month ORR of group B (P=0.047, OR 10.754, 95% CI: 1.031-112.124).No difference was found in side-effects between the two groups (P>0.05) except ATG infusion reaction and serum disease. Mortality was 7.8% (4/51) in group A and no patient died in group B(P>0.1). Summary/Conclusion: CSA plus EPAG had similar response and side effects compared with standard IST plus EPAG in patients with newly diagnosed AA. Figure 1 Hematological responses at 3, 6 and 12 months after ATG combined with CSA and TPO-RA treatment and CSA plus TPO-RA treatment. Keywords: ATG, Thrombopoietin (TPO), Aplastic anemia